ORPHENADRINE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H23NO.ClH
Molecular Weight	305.842
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2C

InChI

InChIKey=UQZKYYIKWZOKKD-UHFFFAOYSA-N

InChI=1S/C18H23NO.ClH/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16;/h4-12,18H,13-14H2,1-3H3;1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C18H23NO
Molecular Weight	269.3813
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs. Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular, the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect. Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favorable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. Adverse reactions of orphenadrine citrate are mainly due to the mild anticholinergic action of orphenadrine citrate and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and rarely urticaria and other dermatoses

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H1 receptor 316 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22793499	Antagonist 2849	97.7 µM [IC50]
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9464369	Antagonist 2849	6.0 µM [Ki]
Muscarinic acetylcholine receptor 162 Target ID: CHEMBL2094109 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3353357	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Musculoskeletal pain 10 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdf	Primary		Approved 8583	DISIPAL Approved Use Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date 1957
Quinine-resistant leg cramps 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdf	Primary		Approved 8583	DISIPAL Approved Use Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date 1957

C_max

Value	Dose	Co-administered	Analyte	Population
41.89 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Bioeqr.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ORPHENADRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
49.19 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Bioeqr.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ORPHENADRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1739.15 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Bioeqr.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ORPHENADRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1772.44 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Bioeqr.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ORPHENADRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
21.02 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Bioeqr.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ORPHENADRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
22.29 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Bioeqr.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ORPHENADRINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
7% EXPERIMENT https://www.sciencedirect.com/science/article/pii/S0021967307003342?via%3Dihub			ORPHENADRINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
500 mg 1 times / day steady, oral Highest studied dose Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1220958	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/1220958	Sources: https://pubmed.ncbi.nlm.nih.gov/1220958
2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf
2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf
2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf

AEs

AE	Significance	Dose	Population
Toxic reaction (NOS)	grade 5	2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf
Toxic reaction (NOS)	grade 5	2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf
Toxic reaction (NOS)	grade 5	2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/012157s028lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013055s021lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 926 CYP1A2 2153 CYP2A6 879 CYP2C19 2057 OCT2 779 OCT1 620 MATE1 415 MATE2 267		CYP2B 32

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/25/3/390.long	partial
CYP2A6 911	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/25/3/390.long	partial
CYP2C19 2141	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/25/3/390.long	partial
CYP3A4 2633	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/25/3/390.long	partial
CYP2B6 1160	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/25/3/390.long	strong
CYP2C9 2497	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/25/3/390.long	strong
CYP2D6 2546	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/25/3/390.long	strong
MATE1 416	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257218/	weak [IC50 65 uM]
MATE2 267	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257218/	weak [IC50 >100 uM]
OCT1 656	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257218/	weak [IC50 >100 uM]
OCT2 782	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257218/	yes [IC50 2.5 uM]
CYP2B 41	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/12813002/	yes

Sourcing

Vendor/Aggregator	ID	URL
Aurora Fine Chemicals LLC	K02.874.612	http://online.aurorafinechemicals.com/info?ID=K02.874.612
BLD Pharm	BD63442	http://www.bldpharm.com/products/83-98-7.html
ChemMol	99164358	http://www.chemmol.com/chemmol/99164358.html
Chemspace	CSSB00020618959	https://chem-space.com/CSSB00020618959
Clearsynth	CS-P-00468	https://www.clearsynth.com/en/CSP00468.html
eNovation Chemicals	D111469	https://www.enovationchem.com/ProductDetails.asp?ProductID=D111469
iChemical	EBD71118	http://www.ichemical.com/products/83-98-7.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-7320950210	https://mcule.com/MCULE-7320950210/
Smolecule	S603082	https://www.smolecule.com/products/s603082
THE BioTek	bt-364984	https://www.thebiotek.com/product/others/bt-364984

PubMed

Title	Date	PubMed
Prochlorperazine in childhood: side-effects.	1977	216517
Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes.	2001 Jun	11353758
Acute intoxication with orphenadrine and clozapine.	2001 Nov 15	11731191
Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity.	2002	12373515
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.	2003 Dec 15	14678746
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
Upregulation of cytochromes P450 2B in rat liver by orphenadrine.	2003 Jun	12813002
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003 Nov 17	14612892
Analgesic effects of low-dose intravenous orphenadrine in the state of capsaicin hyperalgesia. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from capsaicin-irritated skin in healthy volunteers.	2004	15553107
Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer.	2004 Jan 12	14710203
Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer.	2004 Jan 12	14710202
Objective high-frequency tinnitus of middle-ear myoclonus.	2004 Mar	15068524
NMDA receptor in nucleus accumbens is implicated in morphine withdrawal in rats.	2004 Nov	15662845
Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease.	2004 Oct	15380487
Alternatives to levodopa in the initial treatment of early Parkinson's disease.	2005	16156677
[Comparative study between botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome.].	2005 Apr	19471828
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.	2005 Feb 27	15799453
Dimemorfan N-demethylation by mouse liver microsomal cytochrome P450 enzymes.	2005 Jul 1	15936348
Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs.	2006 Dec	17274518
Torsades de pointes in congenital long QT syndrome following low-dose orphenadrine.	2006 May	16700864
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer.	2006 May 24	16723016
OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice.	2006 Nov	17132069
Effects of enzyme inducers and inhibitors on the pharmacokinetics of metformin in rats: involvement of CYP2C11, 2D1 and 3A1/2 for the metabolism of metformin.	2006 Oct	16940989
Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery.	2006 Sep	16981050
Acute adverse cutaneous reaction after the concomitant use of venlafaxine and orphenadrine citrate plus paracetamol in a depressed patient.	2006 Sep	16922966
Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction.	2006 Sep	16845130
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.	2007 Apr 20	17339039
Evaluation of enantioselective binding of basic drugs to plasma by ACE.	2007 Aug	17661317
Effect of warnings in a medical journal on the use of orphenadrine.	2008 Aug	18462287
Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration.	2008 Dec	18321539
Genetic and chemical modifiers of a CUG toxicity model in Drosophila.	2008 Feb 13	18270582
Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU.	2008 Jan	18088504
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells.	2008 May	18336846
Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003.	2009 Apr	19390914
Concordant up-regulation of cytochrome P450 Cyp3a11, testosterone oxidation and androgen receptor expression in mouse brain after xenobiotic treatment.	2009 Apr	19226368
Evaluation of luciferin-isopropyl acetal as a CYP3A4 substrate for human hepatocytes: effects of organic solvents, cytochrome P450 (P450) inhibitors, and P450 inducers.	2009 Aug	19451401
The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study.	2009 Feb	19094158
The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents.	2009 Jul 6	19492368
Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders.	2009 Jun 3	19582217
Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients.	2009 Oct 15	19524386
Orphenadrinium picrate picric acid.	2010 Feb 24	21580426
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

Patents

Sample Use Guides

In Vivo Use Guide

Acute musculoskeletal conditions: 100 mg orally twice a day (morning and evening) or 60 mg by intramuscular or intravenous injection. May repeat every 12 hours. Quinine-resistant leg cramps: 100 mg orally at bedtime.

Route of Administration: Other

In Vitro Use Guide

An aliquot (400 mkl) of the brain membrane suspension (0.14 mg of protein), 100 mkl of (-)3H-QNB (0.95 nM) (specific activity 46 Ci/mmol), and 50 mk1 of the competing drugs at various concentrations were preincubated for 10 min. and thereafter incubated for 60 min. at 25C in 50 mM Tris-HC1 buffer (PH 7.4). When binding to heart and lung membranes was studied, 500 nkl of homogenate (protein contents were 0.58 mg and 0.54 mg of rat heart and lung tissue and 0.63 mg of guinea pig lung tissue was added to tubes containing 500 mkl of 50 mM Tris-HC1 buffer (PH 7.4), 100 mk1 of (-)3H-QNB (final concentration 0.4 nM) and 100 mkl of buffer (total binding) or unlabeled Orphenadrine.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:27:53 GMT 2025` Edited by `admin` on `Mon Mar 31 18:27:53 GMT 2025`
Record UNII	UBY910DUXH
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ORPHENADRINE HYDROCHLORIDE

Common Name

English

DISIPAL

Preferred Name

English

ORPHENADRINE HYDROCHLORIDE [EP IMPURITY]

Common Name

English

Orphenadrine hydrochloride [WHO-DD]

Common Name

English

ORPHENADRINE (CHLORIDE)

Common Name

English

ORPHENADRINE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

ORPHENADRINE HYDROCHLORIDE [MART.]

Common Name

English

MEPHENAMIN

Brand Name

English

NSC-82357

Code

English

ORPHENADRINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

ORPHENADRINE HYDROCHLORIDE [VANDF]

Common Name

English

ORPHENADRINE HCL

Common Name

English

Classification Tree Code System Code

WHO-VATC

QN04AB02